Review and research gap identification in genetics causes of syndromic and nonsyndromic hearing loss in Saudi Arabia.

Congenital hearing loss is one of the most common sensory disabilities worldwide. The genetic causes of hearing loss account for 50% of hearing loss. Genetic causes of hearing loss can be classified as nonsyndromic hearing loss (NSHL) or syndromic hearing loss (SHL). NSHL is defined as a partial or complete hearing loss without additional phenotypes; however, SHL, known as hearing loss, is associated with other phenotypes. Both types follow a simple Mendelian inheritance fashion. Several studies have been conducted to uncover the genetic factors contributing to NSHL and SHL in Saudi patients. However, these studies have encountered certain limitations. This review assesses and discusses the genetic factors underpinning NSHL and SHL globally, with a specific emphasis on the Saudi Arabian context. It also explores the prevalence of the most observed genetic causes of NSHL and SHL in Saudi Arabia. It also sheds light on areas where further research is needed to fully understand the genetic foundations of hearing loss in the Saudi population. This review identifies several gaps in research in NSHL and SHL and provides insights into potential research to be conducted.

Design, Synthesis, In Silico and POM Studies for the Identification of the Pharmacophore Sites of Benzylidene Derivatives.

Due to the uneven distribution of glycosidase enzyme expression across bacteria and fungi, glycoside derivatives of antimicrobial compounds provide prospective and promising antimicrobial materials. Therefore, herein, we report the synthesis and characterization of six novel methyl 4,6-O-benzylidene-α-d-glucopyranoside (MBG) derivatives (2-7). The structures were ascertained using spectroscopic techniques and elemental analyses. Antimicrobial tests (zone of inhibition, MIC and MBC) were carried out to determine their ability to inhibit the growth of different Gram-positive, Gram-negative bacteria and fungi. The highest antibacterial activity was recorded with compounds 4, 5, 6 and 7. The compounds with the most significant antifungal efficacy were 4, 5, 6 and 7. Based on the prediction of activity spectra for substances (PASS), compounds 4 and 7 have promising antimicrobial capacity. Molecular docking studies focused on fungal and bacterial proteins where derivatives 3 and 6 exhibited strong binding affinities. The molecular dynamics study revealed that the complexes formed by these derivatives with the proteins L,D-transpeptidase Ykud and endoglucanase from Aspergillus niger remained stable, both over time and in physiological conditions. Structure-activity relationships, including in vitro and in silico results, revealed that the acyl chains [lauroyl-(CH3(CH2)10CO-), cinnamoyl-(C6H5CH=CHCO-)], in combination with sugar, were found to have the most potential against human and fungal pathogens. Synthetic, antimicrobial and pharmacokinetic studies revealed that MBG derivatives have good potential for antimicrobial activity, developing a therapeutic target for bacteria and fungi. Furthermore, the Petra/Osiris/Molinspiration (POM) study clearly indicated the presence of an important (O1δ-----O2δ-) antifungal pharmacophore site. This site can also be explored as a potential antiviral moiety.

Computer Analysis of the Inhibition of ACE2 by Flavonoids and Identification of Their Potential Antiviral Pharmacophore Site.

In the present study, we investigated the antiviral activities of 17 flavonoids as natural products. These derivatives were evaluated for their in vitro antiviral activities against HIV and SARS-CoV-2. Their antiviral activity was evaluated for the first time based on POM (Petra/Osiris/Molispiration) theory and docking analysis. POM calculation was used to analyze the atomic charge and geometric characteristics. The side effects, drug similarities, and drug scores were also assumed for the stable structure of each compound. These results correlated with the experimental values. The bioinformatics POM analyses of the relative antiviral activities of these derivatives are reported for the first time.

An overview of structure-based activity outcomes of pyran derivatives against Alzheimer's disease.

Pyran is a heterocyclic group containing oxygen that possesses a variety of pharmacological effects. Pyran is also one of the most prevalent structural subunits in natural products, such as xanthones, coumarins, flavonoids, benzopyrans, etc. Additionally demonstrating the neuroprotective properties of pyrans is the fact that this heterocycle has recently attracted the attention of scientists worldwide. Alzheimer's Disease (AD) treatment and diagnosis are two of the most critical research objectives worldwide. Increased amounts of extracellular senile plaques, intracellular neurofibrillary tangles, and a progressive shutdown of cholinergic basal forebrain neuron transmission are often related with cognitive impairment. This review highlights the various pyran scaffolds of natural and synthetic origin that are effective in the treatment of AD. For better understanding synthetic compounds are categorized as different types of pyran derivatives like chromene, flavone, xanthone, xanthene, etc. The discussion encompasses both the structure-activity correlations of these compounds as well as their activity against AD. Because of the intriguing actions that were uncovered by these pyran-based scaffolds, there is no question that they are at the forefront of the search for potential medication candidates that could treat Alzheimer's disease.

In vitro potential antiviral SARS-CoV-19- activity of natural product thymohydroquinone and dithymoquinone from Nigella sativa.

Inflammation, oxidation, and compromised immunity all increase the dangers of COVID-19, whereas many pharmaceutical protocols may lead to increased immunity such as ingesting from sources containing vitamin E and zinc. A global search for natural remedies to fight COVID-19 has emerged, to assist in the treatment of this infamous coronavirus. Nigella satvia is a world-renowned plant, an esteemed herbal remedy, which can be used as a liquid medicine to increase immunity while decreasing the dangers of acute respiratory distress syndrome. Thymoqinone (TQ), dithymoqinone (DTQ) and thymohydroquinone (THQ), are major compounds of the essential oil contained in N.sativa. A current study aims to discover the antiviral activity of two compounds, Thymohydroquinone and Dithymoquinone, which are synthesized through simple chemical procedures, deriving from thymoquinone, which happens to be a major compound of Nigella sativa. A half-maximal cytotoxic concentration, "CC50", was calculated by MTT assay for each individual drug, The sample showed anti-SARS-CoV-2 activity at non-cytotoxic nanomolar concentrations in vitro with a low selectivity index (CC50/IC50 = 31.74/23.15 = 1.4), whereby Dimthymoquinone shows high cytotoxicity.

Synthesis, antimicrobial, molecular docking and molecular dynamics studies of lauroyl thymidine analogs against SARS-CoV-2: POM study and identification of the pharmacophore sites.

Nucleoside precursors and nucleoside analogs occupy an important place in the treatment of viral respiratory pathologies, especially during the current COVID-19 pandemic. From this perspective, the present study has been designed to explore and evaluate the synthesis and spectral characterisation of 5́-O-(lauroyl) thymidine analogs 2-6 with different aliphatic and aromatic groups through comprehensive in vitro antimicrobial screening, cytotoxicity assessment, physicochemical aspects, molecular docking and molecular dynamics analysis, along with pharmacokinetic prediction. A unimolar one-step lauroylation of thymidine under controlled conditions furnished the 5́-O-(lauroyl) thymidine and indicated the selectivity at C-5́ position and the development of thymidine based potential antimicrobial analogs, which were further converted into four newer 3́-O-(acyl)-5́-O-(lauroyl) thymidine analogs in reasonably good yields. The chemical structures of the newly synthesised analogs were ascertained by analysing their physicochemical, elemental, and spectroscopic data. In vitro antimicrobial tests against five bacteria and two fungi, along with the prediction of activity spectra for substances (PASS), indicated promising antibacterial functionality for these thymidine analogs compared to antifungal activity. In support of this observation, molecular docking experiments have been performed against the main protease of SARS-CoV-2, and significant binding affinities and non-bonding interactions were observed against the main protease (6LU7, 6Y84 and 7BQY), considering hydroxychloroquine (HCQ) as standard. Moreover, the 100 ns molecular dynamics simulation process was performed to monitor the behaviour of the complex structure formed by the main protease under in silico physiological conditions to examine its stability over time, and this revealed a stable conformation and binding pattern in a stimulating environment of thymidine analogs. Cytotoxicity determination confirmed that compounds were found less toxic. Pharmacokinetic predictions were investigated to evaluate their absorption, distribution, metabolism and toxic properties, and the combination of pharmacokinetic and drug-likeness predictions has shown promising results in silico. The POM analysis shows the presence of an antiviral (O1δ-, O2δ-) pharmacophore site. Overall, the current study should be of great help in the development of thymidine-based, novel, multiple drug-resistant antimicrobial and COVID-19 drugs.

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity.

The discovery and development of new potent antimicrobial and antioxidant agents is an essential lever to protect living beings against pathogenic microorganisms and free radicals. In this regard, new functionalized pyrazoles have been synthesized using a simple and accessible approach. The synthesized aminobenzoylpyrazoles 3a-h and pyrazole-sulfonamides 4a-g were obtained in good yields and were evaluated in vitro for their antimicrobial and antioxidant activities. The structures of the synthesized compounds were determined using IR, NMR, and mass spectrometry. The structure of the compound 4b was further confirmed by single crystal X-ray diffraction. The results of the in vitro screening show that the synthesized pyrazoles 3 and 4 exhibit a promising antimicrobial and antioxidant activities. Among the tested compounds, pyrazoles 3a, 3f, 4e, 4f, and 4g have exhibited remarkable antimicrobial activity against some microorganisms. In addition, compounds 3a, 3c, 3e, 4a, 4d, 4f, and 4g have shown a significant antioxidant activity in comparison with the standard butylhydroxytoluene (BHT). Hence, compounds 3a, 4f, and 4g represent interesting dual acting antimicrobial and antioxidant agents. In fact, pyrazole derivatives bearing sulfonamide moiety (4a-g) have displayed an important antimicrobial activity compared to pyrazoles 3a-h, this finding could be attributed to the synergistic effect of the pyrazole and sulfonamide pharmacophores. Furthermore, Molecular docking results revealed a good interaction of the synthesized compounds with the target proteins and provided important information about their interaction modes with the target enzyme. The results of the POM bioinformatics investigations (Petra, Osiris, Molinspiration) show that the studied heterocycles present a very good non toxicity profile, an excellent bioavailability, and pharmacokinetics. Finally, an antiviral pharmacophore (O δ-, O δ-) was evaluated in the POM investigations and deserves all our attention to be tested against Covid-19 and its Omicron and Delta mutants.

Synthesis, biological activity and POM/DFT/docking analyses of annulated pyrano[2,3-d]pyrimidine derivatives: Identification of antibacterial and antitumor pharmacophore sites.

New annulated pyrano[2,3-d]pyrimidine derivatives were synthesized with hydroxyl, methoxy, bromine, nitrile and nitro substituents on its skeleton. The correlated electronic effect of substituents on the magnitude of antibacterial activity was noted. The electron donating substituents (namely; 4-OH, 4-OCH3, 4-Br) and electron withdrawing substituents (4-NO2) on phenyl ring in the pyrano[2,3-d]pyrimidine skeleton exerted different influence on its antimicrobial activity against some Gram-positive and Gram-negative bacteria such as Pseudomonas aureus, E. coli, Staphylococcus aureus, Klebsiella pneumonia and Bacillus cereus. All the pyrano[2,3-d]pyrimidines were characterized by spectroscopic analyses. Antibacterial screening revealed that the presence of heteroaryl, cyano and amino groups on pyrano[2,3-d]pyrimidine skeleton increases its penetrating power on the bacterial cell wall so that the product becomes more biologically active. So the the nature of electron withdrawing or electro-donnor Impact of substituents should be taken in consideration in drug design. Hydrolysis of -CRN to amide restored vital Intramolecular interaction like ortho-nitrophenyl and ONOδ-…NHδ+/amide link, offering a crucial template for antibacterial NH, HO-pharmacophore sites, which ultimately elevated innate antimicrobial profiles. POM combinatorial analysis of tangible electronic contributions due to armed annulated pyrano[2,3-d]pyrimidines concluded their broad antimicrobial activity and viable/prominent drug score index through perspective parameters particularly: inter atomic distance/linkers, steric, electronic, polar parameters, and with a different polarising effect of electron donating/withdrawing environments of substituents. Furthermore, an anti-Kinase pharmacophore site (OCNHCO) was evaluated in continuation of the POM investigations. All synthesized products verified fewer side effects than standard streptomycin, but facile implication in selective cancer media (viz. breast or leucemia still needs to be screened).

Icotinib, Almonertinib, and Olmutinib: A 2D Similarity/Docking-Based Study to Predict the Potential Binding Modes and Interactions into EGFR.

In the current study, a 2D similarity/docking-based study was used to predict the potential binding modes of icotinib, almonertinib, and olmutinib into EGFR. The similarity search of icotinib, almonertinib, and olmutinib against a database of 154 EGFR ligands revealed the highest similarity scores with erlotinib (0.9333), osimertinib (0.9487), and WZ4003 (0.8421), respectively. In addition, the results of the docking study of the three drugs into EGFR revealed high binding free energies (ΔGb = -6.32 to -8.42 kcal/mol) compared to the co-crystallized ligands (ΔGb = -7.03 to -8.07 kcal/mol). Analysis of the top-scoring poses of the three drugs was done to identify their potential binding modes. The distances between Cys797 in EGFR and the Michael acceptor sites in almonertinib and olmutinib were determined. In conclusion, the results could provide insights into the potential binding characteristics of the three drugs into EGFR which could help in the design of new more potent analogs.

In Silico Approach Using Free Software to Optimize the Antiproliferative Activity and Predict the Potential Mechanism of Action of Pyrrolizine-Based Schiff Bases.

In the current study, a simple in silico approach using free software was used with the experimental studies to optimize the antiproliferative activity and predict the potential mechanism of action of pyrrolizine-based Schiff bases. A compound library of 288 Schiff bases was designed based on compound 10, and a pharmacophore search was performed. Structural analysis of the top scoring hits and a docking study were used to select the best derivatives for the synthesis. Chemical synthesis and structural elucidation of compounds 16a-h were discussed. The antiproliferative activity of 16a-h was evaluated against three cancer (MCF7, A2780 and HT29, IC50 = 0.01-40.50 µM) and one normal MRC5 (IC50 = 1.27-24.06 µM) cell lines using the MTT assay. The results revealed the highest antiproliferative activity against MCF7 cells for 16g (IC50 = 0.01 µM) with an exceptionally high selectivity index of (SI = 578). Cell cycle analysis of MCF7 cells treated with compound 16g revealed a cell cycle arrest at the G2/M phase. In addition, compound 16g induced a dose-dependent increase in apoptotic events in MCF7 cells compared to the control. In silico target prediction of compound 16g showed six potential targets that could mediate these activities. Molecular docking analysis of compound 16g revealed high binding affinities toward COX-2, MAP P38α, EGFR, and CDK2. The results of the MD simulation revealed low RMSD values and high negative binding free energies for the two complexes formed between compound 16g with EGFR, and CDK2, while COX-2 was in the third order. These results highlighted a great potentiality for 16g to inhibit both CDK2 and EGFR. Taken together, the results mentioned above highlighted compound 16g as a potential anticancer agent.

Pyrrolizine/Indolizine-NSAID Hybrids: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies.

In the current study, eight new hybrids of the NSAIDs, ibuprofen and ketoprofen with five pyrrolizine/indolizine derivatives were designed and synthesized. The chemical structures of these hybrids were confirmed by spectral and elemental analyses. The antiproliferative activities of these hybrids (5 µM) was investigated against MCF-7, A549, and HT-29 cancer cell lines using the cell viability assay, MTT assay. The results revealed 4-71% inhibition of the growth of the three cancer cell lines, where 8a,e,f were the most active. In addition, an investigation of the antiproliferative activity of 8a,e,f against MCF-7 cells revealed IC50 values of 7.61, 1.07, and 3.16 µM, respectively. Cell cycle analysis of MCF-7 cells treated with the three hybrids at 5 µM revealed a pro-apoptotic increase in cells at preG1 and cell cycle arrest at the G1 and S phases. In addition, the three hybrids induced early apoptotic events in MCF-7 cells. The results of the molecular docking of the three hybrids into COX-1/2 revealed higher binding free energies than their parent compounds 5a,c and the co-crystallized ligands, ibuprofen and SC-558. The results also indicated higher binding free energies toward COX-2 over COX-1. Moreover, analysis of the binding modes of 8a,e,f into COX-2 revealed partial superposition with the co-crystallized ligand, SC-558 with the formation of essential hydrogen bonds, electrostatic, or hydrophobic interactions with the key amino acid His90 and Arg513. The new hybrids also showed drug-likeness scores in the range of 1.06-2.03 compared to ibuprofen (0.65) and ketoprofen (0.57). These results above indicated that compounds 8a,e,f deserve additional investigation as potential anticancer candidates.

Structural variation of the malaria-associated human glycophorin A-B-E region.

BACKGROUND: Approximately 5% of the human genome shows common structural variation, which is enriched for genes involved in the immune response and cell-cell interactions. A well-established region of extensive structural variation is the glycophorin gene cluster, comprising three tandemly-repeated regions about 120 kb in length and carrying the highly homologous genes GYPA, GYPB and GYPE. Glycophorin A (encoded by GYPA) and glycophorin B (encoded by GYPB) are glycoproteins present at high levels on the surface of erythrocytes, and they have been suggested to act as decoy receptors for viral pathogens. They are receptors for the invasion of the protist parasite Plasmodium falciparum, a causative agent of malaria. A particular complex structural variant, called DUP4, creates a GYPB-GYPA fusion gene known to confer resistance to malaria. Many other structural variants exist across the glycophorin gene cluster, and they remain poorly characterised. RESULTS: Here, we analyse sequences from 3234 diploid genomes from across the world for structural variation at the glycophorin locus, confirming 15 variants in the 1000 Genomes project cohort, discovering 9 new variants, and characterising a selection of these variants using fibre-FISH and breakpoint mapping at the sequence level. We identify variants predicted to create novel fusion genes and a common inversion duplication variant at appreciable frequencies in West Africans. We show that almost all variants can be explained by non-allelic homologous recombination and by comparing the structural variant breakpoints with recombination hotspot maps, confirm the importance of a particular meiotic recombination hotspot on structural variant formation in this region. CONCLUSIONS: We identify and validate large structural variants in the human glycophorin A-B-E gene cluster which may be associated with different clinical aspects of malaria.

DFT calculations and POM analyses of cytotoxicity of some flavonoids from aerial parts of Cupressus sempervirens: Docking and identification of pharmacophore sites.

Two known polyphenols named apigenin 7-O-ß-d-glucopyranoside (S1) and querctine-3-O-glucoside (S2), along with another two new compounds apigenin 4'-geranyl-8-glucopyranosyl-7-O-α-glucopyranoside (S3) and apigenin 4'-pernyl-8-glucopyranosyl -7-O-α-glucopyranoside (S4), were isolated from the leaves of Cupressus sempervirens. Structure elucidation of the isolated polyphenols was established on the basis of detailed spectroscopic analysis like 1D and 2D NMR analyses including 1H NMR, 13C NMR, COSY, DEPT, HMQC, UV, and Electron Spray Ionization Mass Spectroscopy (ESI-MS). Density Functional Theory (DFT) of computational, Petra/Osiris/Molinspiration (POM), and docking analyses methods were applied in the structural validation of new isolated compounds. The isolated compounds S1-S4 showed significant cytotoxicity against human hepatocellular liver carcinoma HepG2 cells, MCF-7, HC116 and A549.

Methylene-bearing sulfur-containing cyanopyrimidine derivatives for treatment of cancer: Part-II.

In continuation of our previous work on anticancer and anti-inflammatory agents, a series of 22 novel methylene-bearing sulfur-containing cyanopyrimidine derivatives was synthesized by Biginelli condensation reaction, which was followed by nucleophilic substitution of the chloro group with secondary or tertiary amines. Structural confirmation of these derivatives was attained through different spectral techniques. Then, anticancer evaluation of these compounds was done at the National Cancer Institute. Compounds 4g, 4j, 4k, and 4v demonstrated appreciable results against different cell lines. Among the synthesized compounds, 4g (NSC: 795475) exhibited a growth inhibition (GI) of 81.34% against the NCI-H460 lung cancer cell line, 72.64% against the ACHN renal cancer cell line, and 112.17% against the OVCAR-4 ovarian cancer cell line. Compound 4j (NSC: 795746) was active against U-251 CNS cancer, OVCAR-4 ovarian cancer, and 786-0 and ACHN renal cancer cell lines, with GI of 78.84%, 150.38%, 75.64%, and 86.45%, respectively. The literature supporting the association between cancer and underlying inflammation prompted us to evaluate the four compounds, 4g, 4j, 4k, and 4v, with appreciable anticancer activity for their in vitro anti-inflammatory activity. Cyclooxygenase (COX)-2 inhibition studies were also performed to study the molecular target. To validate the target study, molecular docking studies in the ligand-binding domain of COX-2 (PDB ID: 1CX2) were also performed. Compounds 4g, 4j, and 4k did not show cytotoxicity on RAW 264.7 cells up to 10 µM concentration; however, compound 4v showed cytotoxic effects at 10 µM concentration.

Identification of novel selective Mtb-DHFR inhibitors as antitubercular agents through structure-based computational techniques.

Inhibition of dihydrofolate reductase from Mycobacterium tuberculosis-dihydrofolate reductase (Mtb-DHFR) has emerged as a promising approach for the treatment of tuberculosis. To identify novel Mtb-DHFR inhibitors, structure-based virtual screening (SBVS) of the Molecular Diversity Preservation International (MolMall) database was performed using Glide against the Mtb-DHFR and h-DHFR enzymes. On the basis of SBVS, receptor fit, drug-like filters, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis, 16 hits were selected and tested for their antitubercular activity against the H37 RV strain of M. tuberculosis. Five compounds showed promising activity with compounds 11436 and 15275 as the most potent hits with IC50 values of 0.65 and 12.51 µM, respectively, against the H37 RV strain of M. tuberculosis. The two compounds were further tested in the Mtb-DHFR and h-DHFR enzymatic assay for selectivity and were found to be three- to eight-fold selective towards Mtb-DHFR over h-DHFR with minimum inhibitory concentration values of 5.50, 73.89 µM and 42.00, 263.00 µM, respectively. In silico simulation studies also supported the stability of the protein-ligand complex formation. The present study demonstrates the successful utilization of in silico SBVS tools for the identification of novel and potential Mtb-DHFR inhibitors and compound 11436 ((2,4-dihydroxyphenyl)(3,4,5-trihydroxyphenyl)methanone) as a potential lead for the development of novel Mtb-DHFR inhibitors.

Association between graduates' factors and success rate on the Saudi Pharmacist Licensure Examination: A single-Institution cross-sectional study.

INTRODUCTION: The Saudi Pharmacists Licensure Examination's (SPLE) initial results were revealed in February 2020, which showed enormous inconsistency with the passing rates. Hence, we aimed to investigate the predictors of pharmacy graduates' success rate on the SPLE of a single-college in Saudi Arabia. METHODS: In a cross-sectional study of 2019-graduates, data were collected via-phone interviews and retrieved from the college's database. Graduates' data were retrieved from the college's database, which includes high school grade point average (GPA), General Aptitude Test, Scholastic Achievement Admission Test, preparatory year GPA, pharmacy GPA, and all courses' grades. The data collected via-phone interview includes information that was not recorded in the college's database, such as date of birth, SPLE score, and the number of SPLE attempts. We only included students who agreed to be interviewed and had attempted the SPLE at least once. We developed a prediction model using correlational analyses and stepwise multiple linear regression to examine graduates' factors in predicting success on the SPLE. RESULTS: Out of the 149 graduates, 105 fulfilled the inclusion criteria. Around 84% of them passed the SPLE. Correlation analyses showed a significant direct correlation between preparatory year GPA and pharmacy GPA with SPLE scores (r = 0.228, P = 0.0193 and r = 0.533, P < 0.0001, respectively). In addition, the results showed that all of the four SPLE content areas were positively correlated with SPLE scores (P < 0.0001). The stepwise multivariable regression showed that being a male graduate and scoring high-grade points in pharmacology and therapeutics courses were significantly associated with high SPLE scores (P = 0.0053, P = 0.0256, and P = 0.0001, respectively). CONCLUSION: This single cross-sectional study found that being a male, pharmacology GPA, and therapeutics GPA were significantly associated with a higher SPLE score. Further studies should focus on the GPA cut off below which we should give remediation to improve SPLE passing rate.

Arylpropionic acid-derived NSAIDs: New insights on derivatization, anticancer activity and potential mechanism of action.

NSAIDs displayed chemopreventive and anticancer effects against several types of cancers. Moreover, combination of NSAIDs with anticancer agents resulted in enhanced anticancer activity. These findings have attracted much attention of researchers working in this field. The 2-arylpropionic acid-derived NSAIDs represent one of the most widely used anti-inflammatory agents. Additionally, they displayed antiproliferative activities against different types of cancer cells. Large volume of research was performed to identify molecular targets responsible for this activity. However, the exact mechanism underlying the anticancer activity of profens is still unclear. In this review article, the anticancer potential, structure activity relationship and synthesis of selected profen derivatives were summarized. This review is focused also on non-COX targets which can mediate the anticancer activity of this derivatives. The data in this review highlighted profens as promising lead compounds in future research to develop potent and safe anticancer agents.

An unusual hernia postkidney transplantation led to intermittent ureteric obstruction.

A 53-year-old man underwent a living donor kidney transplantation in the right iliac fossa 25 years prior to presentation. He had been noting an inguinal bugle that became more prominent as the day progressed, and it regressed at night. Upon further investigations, an ultrasound of the allograft revealed moderate-to-severe hydronephrosis. A computed tomography scan revealed herniation of the bladder and part of the transplanted ureter within the supravesical/direct inguinal space. Lichtenstein-like fashion of repair was performed, and the patient continues to enjoy satisfactory graft function with no recurrence. The case illustrates a rare hernia as a late complication of the kidney transplant incision leading to ureteric obstruction and a successful attempt at operative repair.

Prevalence, Pattern, Mortality, and Morbidity of Traumatic Small Bowel Perforation at King Abdulaziz Medical City: A Retrospective Cohort Study.

Introduction Bowel perforation, whether from trauma or other causes, presents with diverse clinical scenarios. Small bowel perforation (SBP), a potentially fatal condition often linked to blunt trauma like motor vehicle accidents, necessitates prompt detection and intervention, crucial for improved outcomes. This study investigated the prevalence, predictors, presentation, diagnostic findings, morbidity, and mortality of traumatic SBP for comprehensive insights. Methodology This was a retrospective cohort study conducted at King Abdulaziz Medical City, Riyadh. A review of 838 cases, which represent all abdominal trauma patients from January 2017 to March 2023, was done. Forty patients who developed SBP and have complete data were included in this study. One case was excluded due to incomplete medical records. Data were collected with the non-probability convenience sampling technique via the BestCare system using a data collection sheet. Data were analyzed with IBM SPSS 29 (IBM Corp., Armonk, NY). Results Out of all abdominal trauma cases (n=838), 40 patients developed SBP (n=40, 4.77%). Males constituted 87.5%, and the most common mechanism was motor vehicle accidents (57.5%). Complications included cardiac arrest, disseminated intravascular coagulation (DIC), and leak (7.5% each). In motor vehicle accidents, SBP primarily affected patients who were in the driver's position (78.3%). Clinical signs at presentation revealed abdominal tenderness (52.5%), abdominal distension (22.5%), and abnormal systolic blood pressure (mean 115.3 mmHg). Linear regression showed gender and age positively associated with morbidity (p=0.474, p=0.543) while BMI exhibited a negative relationship (p=0.314). Logistic regression revealed non-significant predictors of mortality, except for mean initial hematocrit (HCT) (p=0.721, aOR=0.098). Conclusion Our study provides crucial findings on the incidence, patterns, mortality, and morbidity of traumatic bowel perforation, contributing to the existing body of research. The identified prevalence of 4.77% and mortality at 17.5% from the studied population underline the serious impact of this condition, and the 37.5% complication rate observed demonstrates the potential risks involved. The average hospital stay is found to be 14 days, adding further to the disease burden. These findings underscore the importance of specific preventative measures, particularly related to motor vehicle accidents (MVAs), and highlight potential markers for predicting outcomes, such as age, gender, and mean initial HCT. This substantiates the need for further research involving larger cohorts and prospective designs to gain comprehensive insights and establish more robust preventative and treatment strategies.

Evaluating a Modified Use of the Kaiser Permanente Early-onset Sepsis Risk Calculator to Reduce Antibiotic Exposure: a Retrospective Study.

BACKGROUND: Early-onset neonatal sepsis (EONS) remains an important disease entity due to very serious adverse outcomes if left untreated. Lack of diagnostic tools in identifying healthy from diseased neonates, and clinicians' fear of the missing positive-culture sepsis babies, or babies with clinical sepsis have led to overtreating and unnecessary antibiotic exposure. Kaiser Permanente EONS risk calculator is an internally validated tool that can predict EONS. This sepsis risk calculator (SRC) classifies neonates into three subgroups: (1) ill-appearing, (2) equivocal and (3) well-appearing. We propose a modification to this tool that aims to use it solely for well-appearing babies. This modification represents a more conservative approach to decrease antibiotic exposure and offers an alternative for those hesitant to fully implement this tool. METHODS: This is a dual-centre retrospective study where data were extracted from the electronic medical records. Our primary outcome was to validate the modified use of the SRC with a two-by-two table. Specificity, negative predictive value and expected antibiotic reduction were used to evaluate the tool's feasibility. RESULT: Among 770 babies suspected of EONS, the feasibility of the modified use was tested. The expected antibiotic exposure reduction rate on the modification was 40.4% overall. The proposed modification resulted in a specificity and negative predictive value of 99.28% (95% CI: 97.92% to 99.85%) and 99.5% (95% CI: 99% to 99.8%), respectively. CONCLUSION: The modified use of the sepsis risk calculator has shown that it can safely reduce antibiotic exposure in well-appearing babies. The modified use is used as a 'rule out' test that can identify very low risk of EONS babies, and safely minimise antibiotic exposure. Further prospective studies are needed to examine the efficacy of this use, and quality improvement projects are required to evaluate its applicability in different clinical settings.